Viral load independent determinants of HIV pathogenesis

HIV发病机制的病毒载量独立决定因素

• 批准号: 8392097
• 负责人: Tuan Dinh Le
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392097
• 关键词: AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Acute; Address; Admixture; African; Age; Antiviral Therapy; Arts; Award; Basic Science; Blood Platelets; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Candidate Disease Gene; Cell Count; Clinical; Commit; Communicable Diseases; Complex; Computer software; Data; Data Set; Databases; Derivation procedure; Disease; Dissociation; Doctor' s Degree; Eating; Educational process of instructing; Environment; Epidemiologic Studies; Epidemiology; Equation; Evaluation; Event; Faculty; Fostering; Funding; Genetic; Genetic Determinism; Genetic Markers; Genetic Polymorphism; Genomics; Goals; HIV; HIV Infections; HIV-1; Health; Health Sciences; Healthcare; Healthcare Systems; Highly Active Antiretroviral Therapy; Immunologics; Industry; Infection; Influentials; Integration Host Factors; Investigation; Learning; Medicine; Mentors; Mentorship; Monitor; Outcome; Pathogenesis; Patients; Persons; Physicians; Play; Population; Postdoctoral Fellow; Predisposition; Public Health; Publications; Published Comment; Recovery; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Role; Scientist; South Africa; South Texas; Staging; System; T-Cell Activation; Talents; Techniques; Testing; Texas; Time; Training; Training Support; United States National Institutes of Health; Universities; Veterans; Viral Load result; Woman; Work; antiretroviral therapy; base; career; cohort; experience; genetic association; genetic epidemiology; genome wide association study; high risk; improved; innovation; meetings; neutrophil; novel; novel strategies; professor; response; skills; success; tool; trait

DESCRIPTION (provided by applicant): Candidate: I am a U.S. citizen and a non-clinician MD. After completing my MD degree, I completed two terminal degrees: a Masters in Public Health (2004) and a Doctorate in Public Health (2008), both completed from the University of North Texas Health Science Center, Fort Worth. During the time-periods that I was completing my doctorate degree, I served as a teaching assistant, and also provided biostatistical support for a project on HIV antiretroviral therapy at the Dallas VA (11/7-5/2008). I provided biostatistical support for other projects till April 2009 (see resume). In April 2009, I was recruited as a post-doctoral fellow in the VA Center for AIDS and HIV infection at the South Texas Veterans Health Care System (STVHCS) where I have worked under the direct mentorship of Dr. Sunil Ahuja. Under Dr. Ahuja's mentorship I have learnt new biostatistical tools and principles of HIV pathogenesis, and has been conducting genetic-epidemiology research. Because of my high potential, industry and talent I was promoted to an assistant professor on June 1, 2010. I am 2.5 years out from my DrPH. and and I am committed to an independent VA-based career in academic medicine. This CDA-2 will greatly enhance and refine my skills in statistical genetics, epidemiology and biostatistical research that has direct relevance to improving our understanding of HIV pathogenesis and improving health outcomes of VA HIV-infected patients. Environment. Dr. Sunil Ahuja will serve as my primary mentor and will be assisted by additional co-mentors and a career advisory team outlined. Dr. Ahuja is a highly accomplished nationally/internationally-recognized physician scientist who has extensive experience in the training and mentorship of junior faculty. Dr. Ahuja's role as a mentor and scientist was recently recognized by the receipt of the prestigious Doris Duke Distinguished Clinical Scientist Award as part of the goals of this award are to support and train young clinician- and non-clinician scientists. He is also supported by a NIH MERIT award and a VA MERIT award. My training will occur within the context of a highly supportive and intellectually rich scientific environment at the VA HIV/AIDS Center which oversees large Cores (E.g. Genetics core) that will also support my research. Research: There is burgeoning data demonstrating that virologic and immunologic events initiated during primary HIV infection play an influential role in setting the tempo of HIV disease course. For this reason, in this study, I will evaluate a large and intensively monitored acute/early infection cohort for evidence that during the proximal-most stages of HIV infection, immunologic and virologic control are partly dissociated, such that contemporaneous setpoints for CD4 cell counts and viral load are established during early infection. I will use candidate gene and genome-wide association studies to identify genetic determinants that underlie CD4-VL dissociation and factors controlling CD4 cell counts during acute/early infection. These investigations will build on the expertise of the nominee and the strong genetic infrastructure at the STVHCS and will enhance the basic science, translational, biostatistical and epidemiological research at the STVHCS.

描述（由申请人提供）： 候选人：我是美国公民，也是一名非临床医学博士。完成医学博士学位后，我又获得了两个终端学位：公共卫生硕士学位（2004 年）和公共卫生博士学位（2008 年），均在沃斯堡北德克萨斯大学健康科学中心完成。在我完成博士学位期间，我担任助教，并为达拉斯退伍军人管理局的艾滋病毒抗逆转录病毒治疗项目提供生物统计支持（2008 年 7 月 11 日至 5 月）。直到 2009 年 4 月，我为其他项目提供了生物统计支持（见简历）。 2009 年 4 月，我被招募为南德克萨斯退伍军人医疗保健系统 (STVHCS) VA 艾滋病和 HIV 感染中心的博士后研究员，并在 Sunil Ahuja 博士的直接指导下工作。在 Ahuja 博士的指导下，我学习了新的生物统计工具和艾滋病毒发病机制的原理，并一直在进行遗传流行病学研究。由于我的巨大潜力、勤奋和才华，我于 2010 年 6 月 1 日晋升为助理教授。我距离博士学位还有 2.5 年。我致力于在学术医学领域从事基于退伍军人管理局的独立职业。 CDA-2 将极大地增强和完善我在统计遗传学、流行病学和生物统计研究方面的技能，这与提高我们对 HIV 发病机制的理解和改善 VA HIV 感染患者的健康结果直接相关。环境。苏尼尔·阿胡贾 (Sunil Ahuja) 博士将担任我的主要导师，并将得到其他共同导师和职业咨询团队的协助。 Ahuja 博士是一位成就卓著的国内/国际公认的医学科学家，在初级教师的培训和指导方面拥有丰富的经验。 Ahuja 博士作为导师和科学家的角色最近获得了著名的多丽丝杜克杰出临床科学家奖的认可，该奖项的目标之一是支持和培训年轻的临床医生和非临床科学家。他还获得了 NIH 优异奖和 VA 优异奖。我的培训将在退伍军人管理局艾滋病毒/艾滋病中心高度支持和知识丰富的科学环境中进行，该中心负责监督大型核心（例如遗传学核心），这些核心也将支持我的研究。研究：越来越多的数据表明，原发性艾滋病毒感染期间引发的病毒学和免疫学事件在确定艾滋病毒疾病进程的节奏方面发挥着重要作用。因此，在这项研究中，我将评估一个大型且集中监测的急性/早期感染队列，以寻找证据表明在 HIV 感染的最近阶段，免疫学和病毒学控制部分分离，从而 CD4 细胞计数的同期设定点和病毒载量是在早期感染期间建立的。我将利用候选基因和全基因组关联研究来确定 CD4-VL 解离的遗传决定因素以及急性/早期感染期间控制 CD4 细胞计数的因素。这些调查将建立在被提名者的专业知识和 STVHCS 强大的遗传基础设施的基础上，并将加强 STVHCS 的基础科学、转化、生物统计和流行病学研究。